WHO | Disseminated bacille Calmette–Guérin disease in HIV-infected South African infants Disclaimer Disseminated bacille Calmette–Guérin disease in HIV-infected South African infants AC Hesseling a, LF Johnson b, H Jaspan c, MF Cotton c, A Whitelaw d, HS Schaaf c, PEM Fine e, BS Eley f, BJ Marais a, J Nuttall f, N Beyers a & P Godfrey-Faussett g a. Desmond Tutu TB Centre, Stellenbosch University, PO Box 19063, Tygerberg, 7505, South Africa. b. Centre for Actuarial Research, University of Cape Town, Cape Town, South Africa. c. Tygerberg Academic Hospital and Children’s Infectious Diseases Clinical Research Unit, Stellenbosch University, Tygerberg, South Africa. d. Department of Medical Microbiology, University of Cape Town, Cape Town, South Africa. e. Department of Epidemiology and Population Health, London School of Hygiene, London, England. f. Paediatric Infectious Diseases Unit, Red Cross Children’s Hospital, Cape Town, South Africa. g.

Department of Infectious and Tropical Diseases, London School of Hygiene, England. Correspondence to AC Hesseling (e-mail: annekeh@sun.ac.za ). (Submitted: 10 June 2008 – Revised version received: 11 October 2008 – Accepted: 20 October 2008 – Published online: 16 April 2009.) Bulletin of the World Health Organization 2009;87:505-511. doi: 10.2471/BLT.08.055657 Introduction Vaccination with bacille Calmette-Guérin (BCG), a live attenuated strain of Mycobacterium bovis, is almost universally given in sub-Saharan African countries where the brunt of the global burden of paediatric infection with type-1 HIV is concentrated. The Joint United Nations Programme on HIV/AIDS (UNAIDS) estimates that 390 000–420 000 children < 15 years of age acquire HIV infection each year. 1 BCG vaccination is usually given at birth or in the perinatal period.

In 2002, an estimated 75% of the 130 million children born worldwide were vaccinated with BCG. 2 BCG has consistent efficacy for the prevention of disseminated tuberculosis in young children without HIV infection. A recent meta-analysis has shown a summary protective BCG effect of 73% (95% confidence interval, CI: 67–79) against tuberculous meningitis and 77% (95% CI: 58–87) against miliary tuberculosis. 2 In contrast, there is limited evidence that BCG has a protective effect in HIV-infected infants and children. 3 , 4 In South Africa, the reported incidence of culture-confirmed tuberculosis among HIV-infected infants is 1596 per 100 000 (95% CI: 115–2132), a rate 24.2 times higher than among infants not infected with HIV. 5 It is possible that HIV-related suppression of T cells compromises specific T-cell mediated immune responses and reduces BCG efficacy in infants.

Adverse events linked to BCG vaccination range from mild, localized complications to more serious, systemic or disseminated BCG disease in which M. bovis BCG is confirmed in one or more anatomical sites far from both the site of injection and regional lymph nodes. 6 Disseminated BCG disease is associated with a case-fatality rate of > 70% in infants. 6 , 7 By comparison, the background mortality rate among South African HIV-infected infants is 12.2 per 100 person-years (95% CI: 8.2–17.4). 8 Systemic or disseminated BCG disease may be clinically indistinguishable from tuberculosis and can only be confirmed through positive mycobacterial culture species identification, preferably by polymerase chain reaction (PCR) for the RD1 genetic region that is lost during attenuation of BCG. 9 While the documented risk of disseminated BCG disease in non-HIV-infected infants is < 5 per 1 million vaccinees and is associated with rare congenital immune deficiencies, 10 it has been shown to be 1100 to 4170 per 1 million in HIV-infected infants routinely vaccinated at birth.

3 , 11 Consequently, in 2007 the WHO Global Advisory Committee on Vaccine Safety and the Strategic Advisory Group of Experts recommended revising BCG vaccination policy for HIV-infected infants. 12 , 13 This milestone recommendation and the ensuing change in policy 14 have resulted in HIV infection becoming a full contraindication for BCG vaccination in infants, even in those who are asymptomatic at birth and at risk of Mycobacterium tuberculosis infection early in life. In preceding years, WHO advised increasing caution on the use of BCG in HIV-infected children, following case reports of disseminated BCG disease. 3 , 6 , 7 , 15 WHO also called for more epidemiological data on the true impact of serious BCG adverse events and for closer monitoring of these events in areas of high HIV infection prevalence, with a specific focus on distinguishing BCG infection from disease caused by M. tuberculosis.

12 , 13 In light of the limited data available to inform the discussion of BCG risks and benefits in HIV-infected infants, we conducted a multicentre surveillance study to estimate more accurately the population incidence of disseminated BCG disease in HIV-infected infants in a setting where tuberculosis and HIV infection are highly endemic and universal neonatal BCG vaccination is practiced. Methods Study setting and design This multicentre prospective hospital-based surveillance study was conducted between 1 January 2004 and 31 December 2006 in the three paediatric referral hospitals that service the Western Cape Province, South Africa: Tygerberg Children’s Hospital, Red Cross Children’s Hospital and Groote Schuur Hospital. These hospitals have specialist paediatric HIV services and routinely perform mycobacterial culture in children with suspected mycobacterial disease in conjunction with speciation of M. tuberculosis complex isolates. Routine prospective laboratory surveillance for BCG-related adverse events was initiated following earlier case reports of serious BCG complications in HIV-infected infants. 6 In South Africa, universal BCG vaccination of infants at birth was implemented in 1973. Most infants are born in health-care centres. Since 2000, intradermal vaccination with the M.

bovis Danish strain 1331 (Statens Serum Institute, Copenhagen, Denmark) is administered in the right deltoid region. In 2005, neonatal vaccination coverage was 98–99% in the province 16 and the overall tuberculosis incidence was 917 per 100 000 total population. 17 In 2006, the HIV infection prevalence among pregnant women in the public health sector was 15.1% (95% CI: 11.6–18.7). 18 There is a well-established public programme for the prevention of mother-to-child transmission (PMTCT) of HIV. HIV testing is offered universally to women at their first antenatal visit. During 2004–2005, dual therapy with zidovudine and nevirapine was used for PMTCT in both mothers and infants. From 2006 onwards, zidovudine was initiated at 28 weeks of pregnancy rather than 34 weeks.

Currently, women whose CD4+ T-lymphocyte (CD4) count is ≤ 200 cells/mm3 are fast-tracked for highly active antiretroviral therapy (HAART). All HIV-infected women are provided with free milk powder for 6 months if they choose to formula-feed. Infant HIV testing was offered at 14 weeks of age with a single HIV-DNA PCR test and infants were followed for 6 months until discharged from the PMTCT programme. The reported vertical HIV transmission rate varied from 5.4% to 10.4% during the study period, a reflection of variations in the introduction, uptake and performance of PMTCT regimens. The uptake of maternal antenatal HIV testing during 2006 was 93.0%; around 90% of women exclusively fed their infants using formula (data from Western Cape Department of Health). This study was approved by the research ethics committees of Stellenbosch University and the University of Cape Town. Study implementation and reporting adhered to STROBE (Strengthening the Reporting of Observational studies in Epidemiology) guidelines.

19 Incidence of disseminated BCG disease As disseminated BCG disease is predominantly seen in HIV-infected children ≤ 1 year of age and who exhibit rapid progression to advanced HIV disease, 3 , 6 , 7 all HIV-infected children ≤ 1 year of age (infants) diagnosed with disseminated BCG disease during the study period were eligible for inclusion. The incidence of disseminated BCG disease was calculated as previously described. 11 In addition, CIs were derived from multiple sources of uncertainty and actual reported, rather than estimated rates of vertical HIV transmission were used. Two cases were included in a previous report from Tygerberg Children’s Hospital. 11 Case definitions and data collection Systemic or disseminated BCG disease was defined as the isolation of M. bovis BCG from one or more clinical samples − regional lymph nodes, respiratory secretions, blood, bone marrow or cerebrospinal fluid − taken at sites distant from the vaccination site, in the presence of a clinical syndrome consistent with disseminated BCG disease. 6 Patient data were obtained from hospital and laboratory records. Mycobacterial culture and HIV testing were routinely performed at the discretion of attending physicians.

The automated Middlebrook 7H9 broth-based Mycobacterial Growth Indicator Tube culture system (Becton-Dickinson, Hunt Valley, MD, United States) was used for mycobacterial culture; the identification of an isolate as M. bovis BCG was confirmed using a multiplex PCR assay that distinguishes M. bovis BCG from other members of the M. tuberculosis complex. 9 The date on which the mycobacterial culture sample was obtained was used to calculate patient age. Infant HIV infection status was determined using HIV-DNA PCR. Incidence The numerator for calculating the incidence of disseminated BCG disease was the total estimated number of HIV-infected infants diagnosed with such disease at the three study hospitals during the study period. Those with disease caused by M. tuberculosis or nontuberculous mycobacteria were excluded. The denominator was the estimated annual number of HIV-infected BCG-vaccinated infants in Western Cape Province, which was obtained from different data sources in the absence of reliable population data on infants in the province.

Data for the Western Cape from the Actuarial Society of South Africa’s 2003 AIDS and demographic model were used to estimate the total number of person-years of observation for all infants. 20 , 21 This model provides a projection of the population of South Africa by age, sex, race, province and HIV status and allows for the effect of AIDS on mortality and fertility rates. It is calibrated to census data, demographic and health survey data, and data on recorded deaths and HIV infection prevalence in national surveys. The proportion of the total number of person-years of observation that corresponded to HIV-infected infants was estimated using the prevalence of maternal HIV infection in the province in conjunction with vertical HIV transmission rates reported by the PMTCT programme. Finally, the reported BCG vaccination coverage rate was used to estimate the number of HIV-infected BCG-vaccinated infants at risk of disseminated BCG disease. Confidence intervals The CIs for the incidence rates were estimated through a bootstrap approach in which the three key quantities used to calculate the incidence rate were treated as independent random variables.

Values for the number of cases of disseminated BCG disease were sampled from a Poisson distribution that had the same mean as the observed number of cases; values for the HIV prevalence were sampled from β distributions based on means and standard deviations determined from published antenatal prevalence estimates and associated CIs; and values for mother-to-child transmission rates were sampled from β distributions based on reported mother-to-child transmission rates and associated sample sizes. The sampling procedure was repeated 10 000 times for each incidence estimate and bootstrap CIs were obtained using the percentile method. 22 Results In total, 32 cases of disseminated BCG disease were confirmed in HIV-infected infants during the study period: 12 in 2004, 12 in 2005 and 8 in 2006. All were included in the study analysis. No cases were observed in infants without HIV infection or with unknown HIV status. Of HIV-infected infants, 53 had disease due to M. tuberculosis and 11 had disease due to nontuberculous mycobacteria; these were excluded from analysis.

Table 1 shows the number of infants with disseminated BCG disease, the estimated number of infants with HIV infection, and the estimated incidence of disseminated BCG disease in these infants. Figures are for the Western Cape Province for the years 2004–2006. The estimated incidence per 100 000 HIV-infected, BCG-vaccinated infants was as follows: 778 (95% CI: 361–1319) in 2004 (estimated vertical HIV transmission rate: 10.4%); 1300 (95% CI: 587–2290) in 2005 (estimated transmission rate: 6.1%); and 1013 (95% CI: 377–1895) in 2006 (estimated transmission rate: 5.4%). The pooled estimate for the incidence of disseminated BCG disease over the entire study period was 992 per 100 000 (95% CI: 567–1495).

The infants’ mean age at presentation was 9 months (range: 1–12 months); 25 of the 32 infants died, which resulted in an all-cause mortality rate of 78.1%. The median time to death following a diagnosis of disseminated BCG disease was 75 days (range: 0–359 days). html, 3kb Discussion We present population estimates of disseminated BCG disease in routinely vaccinated HIV-infected infants obtained through multicentre prospective surveillance. These data confirm that BCG vaccination in HIV-infected infants poses a risk of disseminated BCG disease that is approximately 3- to 4-fold higher than the earlier preliminary estimates of 110–417 cases per 100 000 infants. 11 The difference in risk estimates is most likely due to the inclusion in the present study of all three provincial referral hospitals instead of just one, as in the earlier study, while the denominator for the incidence calculation was derived by the same method. In addition, we used reported rates for vertical HIV transmission in the study period rather than assumed rates of 5%, 10% and 15% in different scenarios.

11 Our calculation of the CIs for the incidence rates was based on three known sources of uncertainty. Thus, the result is more likely to reflect the true uncertainty of the incidence estimates. The low incidence of disseminated BCG disease found in infants without HIV infection is consistent with other reports. 10 , 11 Our data support recently revised WHO recommendations against vaccinating HIV-infected infants with BCG. However, it is difficult to decide how to defer BCG vaccination selectively in all infants born to HIV-infected women in settings with high burdens of HIV and tuberculosis. The risk of disseminated BCG disease in the relatively small number of HIV-infected infants must be balanced against the risk of not vaccinating infants without HIV infection, who remain the vast majority of infants. 23 Recently, WHO has emphasized that application of the revised BCG vaccination guidelines will depend on local factors, 14 including the risk of exposure to M. tuberculosis, the prevalence of tuberculosis and HIV infection, the efficacy of programmes for PMTCT of HIV, breastfeeding patterns, and the ability to follow up immunized children and perform early virological testing.

Other requirements include a good tuberculosis surveillance system for pregnant women and their infants and well-functioning integrated services for infant immunization and the treatment of HIV-infected children. WHO outlined four specific scenarios that affect the balance of risks and benefits of BCG vaccination in a setting with high tuberculosis and HIV infection burdens and these scenarios are listed in Box 1. Box 1. Four scenarios, outlined by WHO, that affect the balance of risks and benefits of BCG vaccination in settings with high burdens of tuberculosis and HIV infection 14 Infants born to women of unknown HIV status The benefits of BCG vaccination outweigh the risks, and infants should be vaccinated. Infants whose HIV infection status is unknown and who demonstrate no sign or symptom of HIV infection, but who are born to women known to be HIV-infected The benefits of BCG vaccination usually outweigh the risks, and infants should receive the vaccine after consideration of local factors. Infants who are known to be HIV-infected, with or without signs or symptoms of HIV infection The risks of BCG vaccination outweigh the benefits and infants should not receive the vaccine, but they should receive other routine vaccines.

Infants with unknown HIV infection status but who have signs or symptoms of HIV infection and were born to HIV-infected mothers The risks of BCG vaccination usually outweigh the benefits, and children should not be vaccinated during the first few weeks of life, since clinical symptoms of HIV infection typically occur after 3 months of age. However, the vaccine can be given if HIV infection is ruled out by early virological testing. BCG, bacille Calmette-Guérin. Implementation of the revised BCG vaccination guidelines is likely to be challenging, even with well-functioning PMTCT programmes and good diagnostic facilities, as most HIV transmission occurs peripartum or postpartum. The sensitivity of a single HIV-DNA PCR test performed < 48 hours after birth is < 40% but increases to > 90% at 2–4 weeks. 24 In South Africa and many other developing countries, HIV PCR testing is performed only after 6 weeks, if at all.

A key consideration is therefore whether infant vaccination and PMTCT programmes are able to selectively delay the BCG vaccination of HIV-exposed infants until 10–14 weeks after birth, for example, until a negative HIV-DNA PCR test result is obtained at a routine vaccination visit. Delayed vaccination could be combined with an alternative tuberculosis prevention strategy, such as isoniazid treatment. Such an approach would require close collaboration with other health programmes and an integrated PMTCT and infant vaccination programme with adequate follow-up. Better prevention of maternal and infant HIV infection and more rapid access to HAART for those infected is likely to reduce the infant population at risk of disseminated BCG disease as well as the risk of severe vaccine complications in HIV-infected infants. The International Union against Tuberculosis and Lung Disease BCG Working Group has recently issued a consensus statement on the use of BCG vaccination in countries where HIV infection and tuberculosis are highly prevalent.

25 Although data on the risk of disseminated BCG disease in infants on HAART are lacking, a recent study demonstrated that giving HAART to HIV-infected infants ≤ 12 weeks of age reduced all-cause mortality and tuberculosis in the first year of life, unlike deferring HAART until standard HIV symptomatic or CD4 criteria were met. 8 In addition, the incidence of regional BCG complications was lower. 26 The available data therefore indicate a considerable risk of both tuberculosis and serious BCG complications in HIV-infected infants, while there is little evidence that BCG vaccination is beneficial in such infants. In contrast, most infants without HIV infection benefit from BCG vaccination and are at a low risk of serious vaccine complications. Little is known about the protective efficacy of BCG vaccination in infants exposed to HIV but not HIV-infected or who may be at high risk of tuberculosis because of immunological factors or a high maternal risk of tuberculosis. 27 , 28 , 29 BCG vaccination should be offered to HIV-unexposed infants once HIV infection has been ruled out. The study has several limitations.

Firstly, it is likely that numerator data were considerably underestimated, as not all HIV-infected infants with disseminated BCG disease in the province would have been referred to and investigated in the three study hospitals. In addition, cases may have been missed because mycobacterial disease in children is usually paucibacillary. Secondly, the denominator – the number of BCG‑vaccinated HIV-infected infants – may have been overestimated. In particular, HIV infection prevalence estimates were obtained only for pregnant women attending public health facilities; the prevalence is likely to be lower in those attending private health facilities, among whom vertical transmission will also be lower due to better access to treatment. On the other hand, the denominator may have been underestimated, as it was derived using vertical HIV transmission rates reported by the provincial PMTCT programme, which may have been biased by incomplete uptake of maternal HIV testing and PMTCT, loss to follow-up, inadequate testing of HIV-exposed infants or missing data. In 2006, an estimated 93% of mothers were tested for HIV and 74.7% of infants were tested at or after 14 weeks.

The large CIs reported in the present study reflect uncertainties in the vertical HIV transmission rate and maternal HIV infection prevalence. Our survey should also be replicated in other settings with different levels of mycobacterial exposure and susceptibility to tuberculosis and HIV infection. In our study, disseminated BCG disease was due to Danish strain 1331 BCG. Vaccine strain may influence BCG-related adverse events and should be considered when these are monitored and reported. 30 , 31 We did not have data available on the incidence of tuberculosis among non-vaccinated HIV-infected infants, since routine vaccination coverage was almost universal. In conclusion, the risk of disseminated BCG disease was high in HIV-infected infants routinely vaccinated at birth in a setting with high tuberculosis and HIV burdens and a well-functioning PMTCT programme. However, there are operational obstacles to selectively deferring BCG vaccination in infants born to HIV-infected women. Since not vaccinating an infant who is exposed to HIV but remains uninfected may increase the risk of disseminated tuberculosis, BCG vaccination should continue in settings where HIV infection and tuberculosis are both highly endemic until it is feasible to implement a policy of selective vaccination.

Clear goals should be established for the implementation of safe vaccination practices in HIV-infected infants and for reducing the burden of maternal and infant tuberculosis. More data are needed on the protective effect of BCG vaccination in HIV-infected infants and in HIV-exposed uninfected infants, as well as on the operational feasibility of deferred BCG vaccination in HIV-exposed infants. Safe and effective antituberculosis preventive strategies, including effective vaccines, are urgently needed for HIV-infected infants. ■ Acknowledgements We thank Wendy Brittle for completing mycobacterial culture, Robert Gie for helpful critical comments and the Western Cape provincial PMTCT and EPI programmes (especially Pauline Pieters and Fawzia Desai) for providing HIV and vaccination data. This work is in partial fulfilment of a PhD thesis. Funding: The Harry Crossley Foundation, Stellenbosch University, provided limited project funding. AC Hesseling was funded by a Commonwealth Scholarship. Competing interests: None declared. References Introduction BCG vaccine BCG vaccine is a live bacterial vaccine given for protection against tuberculosis, mainly severe forms of childhood tuberculosis.

It stands for Bacillus Calmette Gurrain, the strain of bovine tuberculosis used in the vaccine & attenuated by French scientists Calmette & Gurrain. BCG is given anytime from birth to 15 days of life along with the zero dose of oral polio vaccine. It is to be given to all children as part of EPI schedule as recommended by Govt. of India. Storage and Preparation BCG vaccine is available as a lyophilized powder in an ampoule. Diluent used is buffered saline that is available separately. It is available in a multidose ampoule containing 20 doses. BCG vaccine stocks can be stored frozen in freezer compartment. Working stock can be stored in the chiller compartment. Even diluents should be stored in the refrigerator's lower racks at 2-80C. BCG vaccine ampoules should be cut with a file very slowly & not snapped open because it has vacuum inside or else the glass will splinter and fly if cut very suddenly. It may be safer to hold the ampoule in a cloth to avoid injury should the glass splinter. Once prepared, BCG vaccine should be used within 2-3 hours & discarded thereafter.

Dosing BCG vaccine is given intradermally i.e. in the layers of skin using 26 no. needle. It is given conventionally over left deltoid area (to differentiate it from small pox vaccine scar, which was conventionally given over right deltoid area). 0.1 ml of vaccine is given using BCG syringe which is a 1 ml. glass syringe with steel plunger to identify it so that it is not used for any other purpose. A wheal or swelling of 6 mm is raised above the surface. No spirit or antiseptic should be applied over the site before injection. Good bath with soap and water is enough to clean the local injection site. At the most one can use normal saline to clean the area. Neither Govt. of India nor Indian Academy of Pediatrics recommends a booster dose of BCG in India. Some countries like in Gulf recommend one or more booster doses. Efficacy In a country like ours where tuberculosis is endemic, children catch the germs early in life & develop primary complex.

In children younger than 3-5 years of age, this can spread & lead to severe & serious forms of childhood tuberculosis like tuberculous meningitis , disseminated tuberculosis, miliary tuberculosis, tuberculosis of organs like bones, urinary tract etc. BCG being live vaccine itself induces a benign primary complex, which leads to some immunity. Such a child when comes in contact with a patient with tuberculosis can still catch the wild germ and develop primary complex, but the spread will be mostly prevented by previous BCG immunity. Hence such children will not develop serious forms of childhood tuberculosis. Such children when they grow as adults can catch tuberculosis again & develop adult form of tuberculosis which is a different type of tuberculosis altogether. This adult type of tuberculosis is not prevented by BCG. Hence BCG does not prevent primary complex but prevents spread of the primary complex & hence the severe forms of childhood tuberculosis. This explains the outcome of the famous Chingleput trial on BCG vaccine efficacy, which failed to show the protective efficacy of BCG against adult type of tuberculosis. Incidentally BCG also cross protects against leprosy & the efficacy is 20%.

Reaction to BCG Immediately after the BCG vaccine there is a small swelling at the injection site which persists for 6-8 hours. After that the swelling disappears & the injection site looks normal. After 6-8 weeks a swelling reappears which looks like a mosquito bite. It grows in size & forms a nodule which breaks open & discharges some fluid & forms an ulcer. The ulcer heals by forming a scar. The whole process takes 2-5 weeks. Some times this process of ulceration & healing recurs 2-3 times. Ultimately the typical puckered scar is formed which remains for lifetime. Injection site should not be pressed or rubbed. It should not be fomented. Nothing needs to be applied locally. Infact, bath with soap and water should suffice even when it has ulcerated. If ulceration occurs within 7 days of injection, one must report to the doctor, as it may be a sign of tuberculosis in the child. Complications BCG does not lead to fever. Hence search for another cause & treat accordingly.

In 1-2 % of vaccinees, local lymphadenitis can occur involving axillary lymph nodes or rarely supraclavicular gland, especially if injection is given very high over arm. In children with immune compromised state like AIDS, BCG can lead to progressive systemic disease. Site of BCG vaccine As we saw before, 1-2% of children develop local BCG lymphadenitis. If that happens following injection over thigh, it will involve superficial & deep inguinal lymph nodes, which can prove dangerous. Also, by convention BCG scars are looked for over the left arm & hence it is easier to recognize for the doctor when parents do not remember whether BCG was given in the past or not. Hence BCG should only be given over left arm & nowhere else. BCG adenitis ocal lymphadenitis can occur due to superadded infection over BCG ulcer. One should try oral antibiotics & anti-inflammatory with good local hygiene (Soap & water). If the lymph node does not shrink or disappear, it is true BCG lymphdenitis.

In these cases if the size of node is less than 10mm - 15mm, if it is firm, non-painful & not matted; no treatment is required & only observation is required. It will usually disappear on its own in the next few months time. If the glands are bigger than 15mm, soft, fluctuating with signs of inflammation or softening, painful and matted or if already an abscess has formed with or without discharge, treatment is definitely required. One can either remove the entire gland surgically or try a course of anti-tuberculous drugs in form of Isoniazid 5 mg/kg/day & Rifampicin 10mg/kg/day on empty stomach for a period of 3-6 months. BCG not given at birth BCG should be given as early as possible in life, before child comes in contact with tuberculosis. It can be given up to 5 years of age. If it is given beyond 6 months it is preferable to do a prior Mantoux test to see if the patient is already sensitized to tuberculosis. If patient is already sensitized as shown by positive MT, BCG is not necessary.

If prior MT is not done, at least check for accelerated reaction to BCG in first week after vaccination which may suggest presence of tuberculosis in the child. BCG and developed countries In developed countries like USA, very few cases of tuberculosis occur. As BCG does not prevent primary complex or the adult type of tuberculosis no benefit will be derived by routine BCG vaccination in such countries. In fact BCG can interfere with interpretation of Mantoux test done subsequently. Hence BCG is not recommended in USA routinely. With the spread of HIV, incidence of tuberculosis is rising in USA. Under such circumstances they may have to reconsider about routine BCG vaccination. No BCG scar post vaccination Formation of scar is neither necessary nor is the only indication of success of BCG vaccine. However it is the only simple & convenient way of determining success of BCG vaccine. It may take 3-6 months for the scar to form. If no scar is visible at all after 6 months one needs to do Mantoux test. If negative, one should give repeat BCG. Can BCG be given with other vaccines? BCG can be given with other vaccines.

In fact, BCG is given along with zero dose of OPV & 1st Dose of Hepatitis B vaccine at birth. As measles can depress cell mediated immunity & as BCG induces cell mediated immunity BCG should not be given along with measles or MMR Contributor Information and Disclosures Consultant Pediatrician, Hinduja Hospital, B J Wadia Hospital for Children, Mumbai, India First Created : 1/9/2001 CDC | TB | Fact Sheets - BCG Vaccine Fact Sheets BCG Vaccine Introduction BCG, or bacille Calmette-Guerin, is a vaccine for tuberculosis (TB) disease. Many foreign-born persons have been BCG-vaccinated. BCG is used in many countries with a high prevalence of TB to prevent childhood tuberculous meningitis and miliary disease. However, BCG is not generally recommended for use in the United States because of the low risk of infection with Mycobacterium tuberculosis, the variable effectiveness of the vaccine against adult pulmonary TB, and the vaccine’s potential interference with tuberculin skin test reactivity. The BCG vaccine should be considered only for very select persons who meet specific criteria and in consultation with a TB expert. Recommendations Children.

BCG vaccination should only be considered for children who have a negative tuberculin skin test and who are continually exposed, and cannot be separated from, adults who Are untreated or ineffectively treated for TB disease (if the child cannot be given long-term treatment for infection); or Have TB caused by strains resistant to isoniazid and rifampin. Health Care Workers. BCG vaccination of health care workers should be considered on an individual basis in settings in which A high percentage of TB patients are infected with M. tuberculosis strains resistant to both isoniazid and rifampin; There is ongoing transmission of such drug-resistant M. tuberculosis strains to health care workers and subsequent infection is likely; or Comprehensive TB infection-control precautions have been implemented, but have not been successful. Health care workers considered for BCG vaccination should be counseled regarding the risks and benefits associated with both BCG vaccination and treatment of Latent TB Infection (LTBI). Contraindications Immunosuppression. BCG vaccination should not be given to persons who are immunosuppressed (e.g., persons who are HIV infected) or who are likely to become immunocompromised (e.g., persons who are candidates for organ transplant).

Pregnancy. BCG vaccination should not be given during pregnancy. Even though no harmful effects of BCG vaccination on the fetus have been observed, further studies are needed to prove its safety. Testing for TB in BCG-Vaccinated Persons The tuberculin skin test (TST) and blood tests to detect TB infection are not contraindicated for persons who have been vaccinated with BCG. Tuberculin Skin Test (TST). BCG vaccination may cause a false-positive reaction to the TST, which may complicate decisions about prescribing treatment. The presence or size of a TST reaction in persons who have been vaccinated with BCG does not predict whether BCG will provide any protection against TB disease. Furthermore, the size of a TST reaction in a BCG-vaccinated person is not a factor in determining whether the reaction is caused by LTBI or the prior BCG vaccination. (See below for specific guidance on skin test results.) TB Blood Tests. Blood tests to detect TB infection, unlike the TST, are not affected by prior BCG vaccination and are less likely to give a false-positive result.

Treatment for LTBI in BCG-Vaccinated Persons Treatment of LTBI substantially reduces the risk that TB infection will progress to disease. Careful assessment to rule out the possibility of TB disease is necessary before treatment for LTBI is started. Evaluation of TST reactions in persons vaccinated with BCG should be interpreted using the same criteria for those not BCG-vaccinated.

Persons in the following high-risk groups should be given treatment for LTBI if their reaction to the TST is at least 5 mm of induration or they have a positive result using a TB blood test: HIV-infected persons Recent contacts to a TB case Persons with fibrotic changes on chest radiograph consistent with old TB Patients with organ transplants Persons who are immunosuppressed for other reasons (e.g., taking the equivalent of >15 mg/day of prednisone for 1 month or longer, taking TNF-a antagonists) In addition, persons in the following high-risk groups should be considered for treatment of LTBI if their reaction to the TST is at least 10 mm of induration or they have a positive result using a TB blood test: Recent arrivals (less than 5 years) from high-prevalence countries Injection drug users Residents and employees of high-risk congregate settings (e.g., correctional facilities, nursing homes, homeless shelters, hospitals, and other health care facilities) Mycobacteriology laboratory personnel Persons with clinical conditions that place them at high-risk for developing TB disease (e.g., diabetes) Children less than 4 years of age, or children and adolescents exposed to adults in high-risk categories Persons with

 no known risk factors for TB may be considered for treatment of LTBI if their reaction to the tuberculin test is at least 15 mm of induration or they have a positive result using a TB blood test.

Targeted skin testing programs should only be conducted among high-risk groups. All testing activities should be accompanied by a plan for follow-up care for persons with TB infection or disease. Additional Information HIV & AIDS Information :: BCG vaccination causes immune activation of CD4 T-cells in infants BCG vaccination causes immune activation of CD4 T-cells in infants Heather Jaspan. © IAS/Deborah W. Campos - Commercialimage.net Lesley Odendal Published: 31 July 2012 BCG vaccination, routinely given at birth to protect from tuberculosis (TB), causes an immune-activation of CD4 T cells, the HIV target cells, according to a South African study presented at the Nineteenth International AIDS Conference in Washington DC. This immune activation may increase the risk of infant HIV infection through breastfeeding, particularly in cases where the infant is not receiving antiretroviral prophylaxis or where the mother is not taking fully suppressive antiretroviral therapy. The BCG vaccine is given routinely to infants in settings where TB is endemic and is recommended for HIV-positive children in South African treatment guidelines. The BCG vaccine has been shown to be a safe and effective vaccination against disseminated TB in children without HIV.

Although it is associated with a 1% risk of disseminated disease in HIV-positive children, it is still recommended to be administered to all infants at birth since their HIV status is often only definitively known once they are 4 to 6 weeks old. The study randomised 118 HIV-exposed, uninfected infants from Khayelitsha, a large township outside of Cape Town, where the antenatal HIV-prevalence is 30%. 62 infants were given the BCG vaccination at birth as per recommended guidelines, while 56 infants were given their BCG vaccinations at the age of 8 weeks. Blood was collected at birth, 2 weeks, 6 weeks, and 8 weeks for analysis. The results at 6 weeks showed significantly higher HLA-DR expression on CD4 T cells among the infants who had received BCG at birth, compared with those in the delayed group (p=0.024). The expression of HLA-DR on regulatory T cells correlates positively with immune activation in HIV.

In addition, the results at 6 weeks showed significantly higher CCR5, HLA-DR and CD38 co-expression on CD4 T cells in infants who received BCG at birth compared with those in the delayed group (p=0.01). The CCR5 agonist, MIP-1-beta, was significantly higher at 6 weeks in the plasma of unvaccinated infants (p =0.02). There was no difference in the activation of CD8 T cell activation between activation between BCG-vaccinated and unvaccinated infants. The immune activation of CD4 T cells places breastfed infants especially at an increased risk of HIV infection and disease progression. 39% of mother-to-child HIV transmission is caused by breastfeeding from HIV-infected mothers. However, formula feeding is associated with morbidity and mortality in sub-Saharan Africa and breastfeeding is therefore recommended. There was no significant difference between the groups in the median maternal CD4 count, the mean infant birth weight, infant gender or whether or not the infants were breastfed or formula fed. Although other vaccinations given at 6 weeks are associated with increase in activation, the immune activation effect of BCG is sustained at 8 weeks.

“We think these data have important implications both for the timing of infant BCG vaccination in HIV-exposed infants and for perhaps the use of live replication competent bacteria as HIV and other vaccine vectors in these infants,” said Dr Heather Jaspan, one of the authors of the study. Further research regarding the risks and benefits of BCG vaccination in HIV-exposed infants is needed to inform policy and practice. Reference Jaspan H et al. BCG Vaccination at Birth Induces Non-Specific CD4 T-Cell Activation in HIV-Exposed South African Infants. 19th International Conference on AIDS, abstract FRLBC04, Washington, DC, July 2012. View the abstract on the conference website. View webcast of the conference session. In partnership with UNICEF

Question: The BCG vaccine gives immunity against which disease?
Answer: TUBERCULOSIS